1. Academic Validation
  2. Nodakenin alleviates ovariectomy-induced osteoporosis by modulating osteoblastogenesis and osteoclastogenesis

Nodakenin alleviates ovariectomy-induced osteoporosis by modulating osteoblastogenesis and osteoclastogenesis

  • Eur J Pharmacol. 2023 Oct 20:176121. doi: 10.1016/j.ejphar.2023.176121.
Chunxiao Liu 1 Mengdi Zhao 2 Jingyue Chen 3 Liwen Xu 3 Kaiying Wang 3 Guangyu Li 4
Affiliations

Affiliations

  • 1 Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, China; College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, China.
  • 2 College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun, China.
  • 3 Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, China.
  • 4 College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, China. Electronic address: [email protected].
Abstract

Osteoporosis, a systemic bone disease defined by decreased bone mass and deterioration of bone microarchitecture, is becoming a global concern. Nodakenin (NK) is a furanocoumarin-like compound isolated from the traditional Chinese medicine Radix Angelicae biseratae (RAB). NK has been reported to have various pharmacological activities, but osteoporosis has not been reported to be affected by NK. In this study, we used network pharmacology, molecular docking and molecular dynamics simulation techniques to identify potential targets and pathways of NK in osteoporosis. We found that NK treatment significantly promoted osteogenic differentiation of BMSCs while activating the PI3K/Akt/mTOR signalling pathway by measuring Alkaline Phosphatase activity and the expression of various osteogenic markers. In contrast, LY294002, an inhibitor of PI3K, reversed these changes and inhibited the osteogenic differentiation-enabling effect of NK. Meanwhile, prevent the Akt and NFκB signalling pathways by down-regulating c-Src and TRAF6 thereby effectively inhibiting RANKL-induced osteoclastogenesis. In addition, oral administration of NK to mice significantly elevated bone mass and ameliorated ovariectomized (OVX)-mediated bone microarchitectural disorders. In conclusion, these data suggest that NK attenuates OVX-induced bone loss by enhancing osteogenesis and inhibiting osteoclastogenesis.

Keywords

Nodakenin; Osteoblast formation; Osteoclastogenesis; Osteoporosis.

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